Detection of False Positives From First-trimester Preeclampsia Screening (StopPRE) at the Second-trimester of Pregnancy

Sponsor

Hospital Universitari Vall d'Hebron Research Institute (Other)

Overall Status

Completed

CT.gov ID

NCT03741179

Collaborator

(none)

974

Enrollment

Location

Arms

29.4

Actual Duration (Months)

33.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Pregnant women at a higher risk for pre-eclampsia (PE) should be offered preventive daily treatment with acetylsalicylic acid (ASA) started before 16 weeks of gestation. To select patients at higher risk for PE, multiparametric assessment combining maternal history, biochemical factors and biophysical factors should be used during the first trimester of pregnancy. Multiparametric risk assessments have a detection rate for early-onset PE around 80% at a false positive rate of 10%. Owing to the low prevalence of early-onset and preterm PE, more than 90% of patients considered at high risk, at the first-trimester screening, will not eventually develop PE. Thus, ASA treatment would be innecessary and could be safely discontinued in these patients.

The sFlt-1 to PlGF ratio has a high negative predictive value for PE during the second and third trimester of pregnancy. Thus, it could be used to detect false-positive patients from the first-trimester screening.

This is a multicentric, randomized, open, parallel, controlled, phase III trial, where 1,080 patients under treatment with ASA for being at high risk for preeclampsia from the first-trimester screening, will be candidates to participate. Patients with a sFlt-1/PlGF <38, from 24 to 27+6 weeks of gestation will be randomized at a 1:1 ratio and allocated to either continue ASA until 36 weeks or to stop ASA treatment.

Condition or Disease	Intervention/Treatment	Phase
Pre-Eclampsia	Drug: ASA-withdrawn group	Phase 3

Detailed Description

The main objective of the study is to demonstrate that in patients considered to be at high risk for PE (from the first-trimester screening) and with sFlt-1/PlGF ratio <38, between 24+0 and 27+6 weeks, the incidence of preterm PE, after cessation of the treatment with ASA, will not be superior to that of the control group.

Study Design

Study Type:

Interventional

Actual Enrollment :

974 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A phase III, multicentric, Randomized, open-label, parallel-group clinical trialA phase III, multicentric, Randomized, open-label, parallel-group clinical trial

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase III, Multicentric, Randomized, Open-label, Parallel-group Clinical Trial to Detect False Positives From First-trimester Preeclampsia Screening (StopPRE) at the Second-trimester of Pregnancy

Actual Study Start Date :

Aug 20, 2019

Actual Primary Completion Date :

Jan 30, 2022

Actual Study Completion Date :

Jan 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ASA-withdrawn group ASA treatment will be withdrawn if patients present an sFlt/PlGF < 38 at 24+0-27+6 weeks of gestation.	Drug: ASA-withdrawn group Patients whith sFlt/PlGF ratio < 38 at 24+0-27+6 weeks will be randomized into two arms of the trial. Patients allocated in the experimental arm will stop the ASA treatment. Other Names: sFlt y PlGF ratio less than 38.
No Intervention: ASA group ASA treatment will continue until 36 weeks of gestation if patients present an sFlt/PlGF ratio < 38 at 24+0-27+6 weeks of gestation.

Arm

Intervention/Treatment

Experimental: ASA-withdrawn group

ASA treatment will be withdrawn if patients present an sFlt/PlGF < 38 at 24+0-27+6 weeks of gestation.

Drug: ASA-withdrawn group

Patients whith sFlt/PlGF ratio < 38 at 24+0-27+6 weeks will be randomized into two arms of the trial. Patients allocated in the experimental arm will stop the ASA treatment.

Other Names:

sFlt y PlGF ratio less than 38.

No Intervention: ASA group

ASA treatment will continue until 36 weeks of gestation if patients present an sFlt/PlGF ratio < 38 at 24+0-27+6 weeks of gestation.

Outcome Measures

Primary Outcome Measures

Rate of preterm pre-eclampsia in both arms of the study (ASA vs no ASA). [From 24+0 weeks of gestation onwards]
Rate of pre-eclampsia <37 weeks in pregnant women at high-risk for early-onset PE from the first-trimester screening and ratio sFlt-1/PlGF<38 between 24-27+6 weeks of gestation in both arms of the study (ASA vs no ASA).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients older than 18 years old
Gestational age between 24+0 and 27+6 weeks
Single pregnancy
High-risk for pre-eclampsia from the first-trimester screening for pre-eclampsia
ASA treatment started before or at 16+6 weeks of gestation
Maternal sFlt-1/PlGF ratio at 24+0-27+6 weeks of gestation
Signed informed consent

Exclusion Criteria:

Multiple pregnancy
Dead and/or fetal polymalformation, including also any fetal genetical and/or chromosomic disease.
Von Willebrand disease.
ASA intolerance and /or allergy
Peptic ulcer
ASA compliance <50% before inclusion
Patients with misunderstanding or not able to understand the protocol, including also any condition which could compromise the compliance of the protocol, according to the investigator's opinion.
No signature of the informed consent